The overall goal of this Center is to establish an organization for the neuropsychoendocrinological study of the major mental disorders of adults and children which form the hard core of mental health problems. In adults these include depession, mania, alcoholism, schizophrenia and the mental syndromes associated with renal dialysis; in children, hyperkinesis, autism, and mental retardation. The theoretical base for these studies consists of the principles of neuroendocrinology and the principles of neurotransmitter physiology. A pituitary response fault (diminished TSH response to TRH) has been identified in some depressed patients and in some conditions the fault is related to the state of illness or to the trait of being at high risk for these illnesses. Parallel pituitary response testing, with TRH, is carried out in psychotic and hyperkinetic children. Related neuroendocrine investigations are addressed to renal dialysis patients who show characteristic mental syndromes. In adult schizophrenia there is dissociation between these axes; TSH response appears to be positively related to baseline cortisol values. In normal controls and in all other diagnostic groups the relationship is negative. The altered relationships may provide a biochemical marker for schizophrenia. The techniques of modern genetics are used to explore relationships between affective disorders and alcoholism and hyperkinetic syndrome. Relatives of probands who show TSH blunting are tested to establish whether the physiological fault is a marker in families for the demonstration of illness. Four disciplines of basic science are brought to bear on problems relevant to clinical goals. These are biochemistry, animal neuroendocrinology, animal psychopharmacology, and peptide behavioral pharmacology. Work in these areas clarifies problems of clinical origin; it also provides findings that suggest clinical intervention. The nexus of related clinical and basic projects provide a basis for rich training and practical experiences for several categories of trainees.